The surface modification of a substrate with a biologically active molecules and synthetic polymers can change the substrate surface properties such as tissue and blood compatibility, lubricity, wettability, permeability, antimicrobial properties that are important to the efficacy and safety of the medical product. Of these surface modification techniques, covalently bonding of molecules that are of specific characteristics is know to have the following advantages. i) This surface modification technique is advantageous in that a stable bond is formed between a surface and the modifier; and ii) Characteristic properties can be exhibited that are attributable to a large difference in affinity for material existing between a covalently bonded and topically coated. The process is often described as ‘grafting’ to differentiate from the surface alternation by ordinary spreading and solidifying.
Various grafting techniques have been proposed for the application of surface grafted polymers having aforementioned advantages by making use of their characteristic properties. Often, two alternative approaches are distinguished: “grafting-to”—attaching polymers to the solid surface, and “grafting-from”—monomers being polymerized from solid surface using an initiation at the surface. See Prucker et al., J. Am. Chem. Soc., 1999: 121: 8766-70. Regardless of which technique is used, the solid surface must have reactive sites in an area accessible to the grafting monomers and polymers. This often requires additional steps of surface preparation prior to the grafting to provide the initiation sites for “grafting-from” reaction or have function groups available for “grafting-to” attachment.
Physical activation of chemical reactions, especially via controlled degradation of polymer on the substrate surface has been attempted in many different ways by using high energy radiation, e.g. β- or electron, plasma, UV irradiation. For example, U.S. Pat. No. 5,094,876 describes the method of modifying the plastic surfaces using gamma or electron beam irradiation induced chemical grafting. The method comprises the steps of pre-soaking the substrate in a monomer or a monomer solution to facilitate diffusion of said monomer or monomers into said plastic surface. The method lacks the chemical interaction of pre-formed substrate with the formed polymer and requires the use of organic solvent to facilitate diffusion of the monomers to the substrate and therefore poses the difficulty of removing the organic solvent afterwards.
WO 01/17575 A1 describes the radiation method of grafting hydrogel onto organic substrates. It involves steps of exposing a substrate to an initiator to generate reactive radical sites on the surface for graft polymerization of monomers immersed in thereby forming covalent bonds between monomer molecules and the substrate at reactive radical sites on the substrate surface. This “grafting-from” method calls for a separate step of surface preparation and may not applicable to many radical inert polymer substrates.
Plasma initiated hydrophilic coating was disclosed in U.S. Pat. No. 7,217,769 B2, wherein a double bond(alkene) monomer such as N-trimethylsilyl-allylamine (TMSAA), ethylene, propylene and allyl alcohol, was first deposited onto the substrate by plasma grafting and thereby attaching a reactive site for subsequent plasma cross-linking of the hydrophilic molecules bearing a “bifunctional spacer” such as α-hydro-ω-hydroxypoly(oxy-1,2-ethanediyl)-bis-(1-hydroxbenzotriazolyl carbonate) (HPEOC). The method requires the plasma deposition of primary or secondary amine for the subsequent coupling reaction with a “bifunctional” spacer and subsequent bio-conjugation with hydrophilic molecules. The covalent bonding of “prime” coating of primary or secondary amine to the substrate is not guaranteed.
The excitation with high energy irradiation has a low selectivity, bond scissions in the volume of substrate surface and sub-surface are inevitable. The excitation with plasma is very surface specific, however, in addition to the requirement of vacuum, the ablation tendency of the base polymer may be significant. Ulbricht et al., J AppL Polym. Sci., 1995, 56:325. Also, the contribution of the high-energy deep-UV radiation during a direct plasma exposure may lead to an uncontrolled degradation process. Ulbricht, Polymer, 2006, 47: 2217-2262. In addition, the delicate topological feature of the surface may be damaged due to the exposure to the irradiation.
Other surface functionalization methods such as oxidative hydrolysis and chemical oxidative etching have also been used to create reactive surface with functional groups such as amino, aldehyde, epoxide, carboxyl, or other reactive groups for subsequent surface modification. These “grafting-to” surface treatments involve harsh condition which may adversely affect the bulk properties and surface morphology.
The above prior arts, regardless of the method being used, requires the steps of surface preparation to create bonding sites, either by chemical treatment to generate radicals on the surface or by physical irradiation activation. Direct coupling on reactive side groups or end groups of the substrate material (e.g. for cellulose derivatives polyamide or polysulfones) has been reported. See Klein, J. Membr. Sci., 2000, 179:1, and Castilho et al., J. Membr Sci., 2000, 172: 269. However, there has been limited success due to the limited availability of reactive functional groups on the surface directly accessible to a surface modifier.